Abstract

Mitotic Catastrophe is the Mechanism of Lethality
for Mutations that Confer Mutagen
Sensistivity in Aspergillus nidulans.
Mutation Research 304:193-202 (1994)
Steven H. Denison and Gregory S. May
Department of Cell Biology, Baylor
College of Medicine, Houston, TX 77030 USA
Summary
We have examined the consequences of treatment with DNA
damaging agents of uvs mutants and the bimD6 mutant of Aspergillus
nidulans. We first established that wild Aspergillus undergoes
a cell cycle delay following treatment with the DNA damaging
agents methyl methanesulfonate (MMS) and ultraviolet light (UV).
We have also determined that strains carrying the bimD6, uvsB110,
uvsH77, uvsF201and the uvsC114 mutations, all of which cause an
increased sensitivity to DNA-damaging agents, undergo a cell cycle
delay following DNA damage. These mutations do not therefore represent
nonfunctional checkpoint mutations in Aspergillus. However, all of the
mutant strains accumulated nuclear defects after the period of delay
following mutagen treatment. The nuclear defects in the uvsB110 and
bimD6 strains following MMS treatment were shown to be dependent on
passage through mitosis after DNA damage, as the defects were
prevented with benomyl. Checkpoint controls responding to DNA
damage are thus able to only temporarily halt cell cycle progression
in response to DNA damage. The conditional bimD6 mutation results in
a defective mitosis at restrictive temperatures. This mitotic defect
is copied with MMS treatment at temperatures permissive for the mitotic
defect. The bimD gene product may perform a role in DNA repair which is
also required in the mitotic cell cycle in the absence of damage due to
mutagen treatment.
gsmay at bcm.tmc.edu